Erythrocyte Na,K pump in uremia. Acute correction of a transport defect by hemodialysis.

Izumo, Hiroko; Izumo, S; Deluise, Mario; Flier, Jeffrey S.

doi:10.1172/jci111455

Cited by 75 publications

(22 citation statements)

References 19 publications

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“…Minkoff Izumo and associates (47) found that there was impaired function of the erythrocyte Na-K ATPase pump in uremia. They suggested that the impairment of the Na-K ATPase pump was due to a nonouabain-like circulating factor which was markedly diminished by acute hemodialysis (47).…”

Section: Discussionmentioning

confidence: 99%

Abnormal sodium transport in synaptosomes from brain of uremic rats.

Fraser¹,

Sarnacki²,

Arieff³

1985

J. Clin. Invest.

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The causes of central nervous system (CNS) dysfunction in uremia are not well known and are not completely reversed by dialysis. This problem was investigated in synaptosomes, which are membrane vesicles from synaptic junctions in the brain. We measured Na uptake under conditions of control, veratridine stimulation, and tetrodotoxin inhibition, in synaptosomes from normal and acutely uremic (blood urea nitrogen, 250 mg/dl) rats. In the control state, maximal Na uptake was 2.2±0.2 and 1.9±03 nmol/mg of protein in normal and uremic synaptosomes, respectively. With veratridine stimulation, Na uptake was increased by 1.9 and 3.6 nmol/mg of protein in normal vs. uremic rats (P < 0.001). The increased veratridine-stimulated Na uptake observed in uremia could be due either to increased membrane permeability to Na or decrease in the Na-K ATPase pump activity. To investigate this, we studied the Na-K ATPase pump function by evaluating uptake of K (using rubidium as a tracer), uptake of Na during ATP stimulation, and inhibition of Rb and Na uptake by ouabain. In uremic rats both Rb uptake and ATP-stimulated Na uptake were significantly less than in normals (P < 0.005). This suggests a defect in the Na-K ATPase pump. Membrane permeability for Na was then evaluated both by measuring initial Na uptake, and with addition of valinomycin. No change in Na uptake pattern was observed with valinomycin, and initial Na uptake was not significantly different in normal versus uremic synaptosomes. These data show that (a) in uremic rats veratridine-stimulated Na accumulation is significantly greater than normal; (b) the increased Na accumulation observed in uremia appears to be due to alterations in Na-K ATPase pump activity, and (c) the

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Section: Discussionmentioning

confidence: 99%

Abnormal sodium transport in synaptosomes from brain of uremic rats.

Fraser¹,

Sarnacki²,

Arieff³

1985

J. Clin. Invest.

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“…Inhibitor substances accumulating in uremia [31], increased serum neuraminidase activity [37], changed erythrocyte membrane fluidity [38], impaired Na-K pump system in the erythrocytes [39] and increased purine/pyrimidine content in uremic hemolysates [40] have all been suggested to contribute to the hemolysis in patients with CRF. In addition to reduced antioxidant potential, artifacts occurring during dialysis, several uremic metabolites [31], oxidative stress due to hexose monophosphate shunt inhibition [23,24] and reduced ATP/ADP ratio due to oxidative metabolism [40] may all contribute to the increased toxic-free radical production in the erythrocytes.…”

Section: Discussionmentioning

confidence: 99%

Oxidant/Antioxidant Status of Erythrocytes from Patients with Chronic Renal Failure: Effects of Hemodialysis

Durak¹,

Kavutçu²,

Çimen³

et al. 2001

Med Princ Pract

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Objective: It has been suggested that oxidative processes may be increased in patients with chronic renal failure (CRF), and that this is a possible factor contributing to the development of anemia and atherosclerosis, characteristic complications of CRF. The aim of this study was to investigate erythrocyte oxidant/antioxidant status in patients with CRF and to elucidate possible effects of hemodialysis on erythrocyte antioxidant system. Methods: Fasting blood samples were obtained from 33 patients with CRF and from 12 healthy controls. Of the patients, 17 subjects were under regular hemodialysis. Values of the activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and antioxidant potential, nonenzymatic superoxide radical scavenger activity (NSSA) and levels of thiobarbituric acid reagent substances (TBARS) were measured in the erythrocytes from both patients and controls. Results: Antioxidant potential and NSSA values were found to be significantly decreased, while TBARS levels were increased in the erythrocytes of patients. SOD activity was found to be unchanged, but GSH-Px and CAT activities were significantly lower in the patient group. Moreover, the erythrocyte TBARS level in the hemodialysis group was higher than in the controls and nonhemodialysis patients. Conclusion: The results suggest that antioxidant potential is reduced due to impaired antioxidant system in erythrocytes from patients with CRF and that oxidant stress causes significant peroxidation. Hemodialysis is determined to further increase oxidative reactions. These changes seem to contribute to the occurrence of some complications of CRF. Therefore, it has been suggested that antioxidant supplementation may give beneficial results for these patients.

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“…Uremic cells may have a higher than normal Na+ content due to increased plasma levels o f'ouabain-like' and 'nonouabain-like' factors [27][28][29], which inhibit the Na+/K+ pump. Increased intracellu lar Na+ content might reduce the electrochemical Na+ gra dient across the cell membrane and thus the driving force for the Na+/H + exchanger activity.…”

Section: Discussionmentioning

confidence: 99%

Lymphocytic Intracellular pH and Na<sup>+</sup>/H<sup>+</sup> Exchanger Activity in Hemodialysis Patients

Rombolà

Colussi²,

Guastoni³

et al. 1995

Am J Nephrol

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We have evaluated intracellular pH (pH_i) and Na⁺/H⁺ exchanger activity in peripheral lymphocytes from 16 patients on regular acetate hemodialysis. All the patients were taking oral NaHCO₃ supplementation (30 mmol/day), to maintain predialysis arterial blood acid-base status within normal range (pH 7.36 ± 0.02, P_HCO3- 23.3 ± 1.2 mM, pC0₂ 40.9 ± 1.4 mm Hg). pH_i was measured, using the fluorescent probe BCECF (2’,7’-bis-carboxyethyl-5,6-carboxyfluorescein), both in nominal absence of bicarbonate (Hepes solution, pH 7.4; n = 10) and in the presence of HCO₃^-/CO₂ buffer system (pH 7.4, [HCO₃^-] 25 mM, PCO₂ 40 mm Hg; n = 6). Predialysis pH_i did not differ from controls when measured in the presence of HCO₃^-/CO₂ (7.28 ± 0.04 vs. 7.29 ± 0.04, p = NS), but was lower in dialysis patients than in normal subjects (7.11 ± 0.04 and 7.20 ± 0.02, respectively; p < 0.05) when measured in Hepes solution. This suggested that bicarbonate-independent pH_i regulation was abnormal in dialysis patients. To further characterize this abnormality of pH_i regulation, lymphocytes were exposed to ethylisopropylamiloride, a specific Na⁺/H⁺ antiporter inhibitor, in Hepes solution; this maneuver induced a significantly lower decrement in pH_i (0.04 ± 0.04 vs. 0.15 ± 0.03, p < 0.05) in dialysis patients than in controls, indicating reduced Na⁺/H⁺ exchanger activity in the patients. The rate of pHi recovery during the first 30 s after induction of various degrees of cell acidification (pH_i range 6.2-7.0), which in the absence of HCO₃^-/CO₂ is dependent on Na⁺/H⁺exchanger activity, was also reduced in the patients as compared to controls (p < 0.001). These findings demonstrate depressed Na⁺/H⁺ exchanger activity in lymphocytes from patients on chronic maintenance hemodialysis; accounting for the lower pHi in Hepes solution. However, this abnormality does not prevent pH_i to be mainteined in the normal range in the presence of the physiological buffer HCO₃^-/CO₂ and possibly in vivo.

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Erythrocyte Na,K pump in uremia. Acute correction of a transport defect by hemodialysis.

Cited by 75 publications

References 19 publications

Abnormal sodium transport in synaptosomes from brain of uremic rats.

Abnormal sodium transport in synaptosomes from brain of uremic rats.

Oxidant/Antioxidant Status of Erythrocytes from Patients with Chronic Renal Failure: Effects of Hemodialysis

Lymphocytic Intracellular pH and Na<sup>+</sup>/H<sup>+</sup> Exchanger Activity in Hemodialysis Patients

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